Daphne odora Exerts Depigmenting Effects via Inhibiting CREB/MITF and Activating AKT/ERK-Signaling Pathways

Abstract

Daphne odora, a blooming shrub, has been traditionally used for various medicinal purposes. However, information on its anti-melanogenic activity and dermal application is limited. In this study, the Daphne odora extract (DOE), with constituents including daphnetin, was used to investigate depigmenting activity and the underlying mechanism of Daphne odora. DOE inhibited in vitro and cellular tyrosinase activity in a dose-dependent manner, and reduced the α-MSH-induced melanin biosynthesis to a control level. The protein expressions of melanin synthesis-related enzymes were also significantly reduced by DOE. Moreover, DOE decreased the phosphorylation of cAMP-response element binding proteins (CREBs) induced by α-MSH in B16F10 cells, while it activated phosphorylated extra-cellular signal-regulated kinases (ERKs) and protein kinase B (AKT) expression. These results suggest that DOE might inhibit the melanogenesis signaling pathways by activating ERK- and AKT-signaling pathways to regulate the expression of CREB and MITF and its downstream pathways. Therefore, DOE could potentially be developed as a depigmenting agent.

Imperatorin Positively Regulates Melanogenesis through Signaling Pathways Involving PKA/CREB, ERK, AKT, and GSK3β/β-Catenin

“…Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), are deeply involved in melanogenesis. In particular, ERK, through its phosphorylation, is responsible for regulating MITF protein stability, i.e., the phosphorylation of MITF decreases its stability and leads to its degradation in proteasomes, and ERK dephosphorylation paradoxically interrupts MITF degradation, thereby activating melanogenesis [ 35 , 36 , 37 ]. Therefore, we next sought to examine whether imperatorin regulates MITF activity via a MAPK pathway.…”

“…The activation of ERK is associated with a reduction in MITF degradation and pigmentation, while the inhibition of ERK increases melanin synthesis. Thus, MAPK signals in melanocytes are promising targets for the development of cosmetics and treatments for skin pigmentation through which MITF expression and stability can be increased [ 35 , 36 , 37 ]. Therefore, we evaluated the effectiveness of imperatorin for the inhibition of the ERK signaling pathway to further explore the molecular mechanisms of melanin synthesis in B16F10 cells.…”

Quercetin 3-O-Galactoside Isolated from Limonium tetragonum Inhibits Melanogenesis by Regulating PKA/MITF Signaling and ERK Activation

“…However, p38 phosphorylation was downregulated, and ERK phosphorylation was increased in the presence of Q3G. Although there are some controversial reports where ERK activation was shown to be increased in parallel with melanin synthesis [ 44 ], most of the studies reported that the phosphorylation of MITF with ERK1/2 led to its ubiquitination and consequent degradation, which resulted in suppressed melanogenesis [ 11 , 12 , 45 ]. The current results confirmed these reports where Q3G treatment elevated ERK phosphorylation.…”

New Mechanistic Insights of Melasma

“…Recent studies have shown that the activation of the Akt signaling pathway contributes to the inhibition of melanogenesis. 63 Intracellular cAMP inhibits phosphatidylinositol 3-kinase (PI3K) and stimulates GSK3β activity, subsequently controlling MITF expression. Activation of GSK3β phosphorylates MITF, thereby enhancing transcriptional activation of tyrosinase-related genes and melanogenesis.…”